Respiratory Pathologies – Tuesday, October 3, 2006

LU anatomy review
~ left side – 2 lobes (cuz heart is in the way)
~ right side – 3 lobes
~ bronchi larger and horizontal on right side of LU – therefore easier to lodge things into
in the LU, psuedostratified ciliated columnar epithelium – these undergo hyperplasia in
smokers
~ metaplasia – changing from one cell type to another cell type (going from
pseudostratified to squamous)
~ in alveoli – simple squamous cells are there for diffusion of CO2 and O2
~ if there is too much pressure on liquid side of lungs, the liquid flows into tissues (which
is alveoli) = pulmonary edema

Atelectasis
~ Shrunken, airless state affecting all or part of LU
~ Collapsed LU – the collapsed lung resorbs and persistant infection causes damage to
the elastic fibers  decrease in ability to maintain size  widening of vessel 
bronchiectasis
~ Acute or chronic
~ Get reduced oxygen = hypoxia
~ Anoxia = NO oxygen (very little chance of this happening in our body)
~ Chronic atelectasis, affected area is often composed of a complex mixture of
airlessness, infection, bronchiectasis, destruction, and fibrosis

Etiology of Atelectasis
Adults – chief cause of acute or chronic atelectasis is bronchial obstruction b/c:
~ 1) bronchial exudates plugs – infection and mucous
~ 2) tumours
~ 3) granulomas
~ 4) foreign bodies
Children – surfactant deficiency
~ Type I (regular cells) and Type II (surfactant secreting) alveoli
~ surfactant reduces surface tension in LU – allows LU to inflate
~ premie babies – have Type II but don’t secrete surfactant yet
~ or if you give them small toys and they swallow it
4 categories
~ 1) resorption – d/t obstruction (main one we’ll see)
~ 2) compression – d/t fluid or air in pleural cavity (between visceral and pleural layer)
~ 3) microatelectasis – in children because d/t decrease surfactant
~ 4) contraction – fibrosis causes LU to contract on itself

Atelectasis Pathophysiology
~ With the bronchial obstruction, there is less fresh air going into the lungs
~ this causes peripheral alveolar gas to be absorbed by the alveolar capillary blood
~ in a few hours, if there is no infection, the lung can shrink or collapse completely
~ Early stages – arterial hypoxemia
~ Slowly proceed into capillary and tissue hypoxia
~ This will lead to transudation of fluid and pulmonary edema
~ fluid in lungs means that there can’t be exchange of O2 and CO2 because the fluid is
pushed into the alveoli
~ the secretions will prevent complete collapse of atelectatic lung
~ But in the case of extensive collapse, diaphragm may elevate, chest wall will flatten,
and HT and mediastinum may shift toward collapsed side
~ bicarbonate is broken into carbon dioxide and water in the LU by carbonic anhydrase
~ bicarbonate is the main extracellular buffer
~ too much CO2 and H2 will cause acidic environment (acidosis)
~ blood pH is tightly regulated around 7.4 – if there is an acid environment, then there
may be an effect on enzymes = BIG problem
~ If the obstruction is removed, air complication may resolve, lung may return to normal
– but this depends on how complicated the infection is
~ If obstruction remains and infection is unresolved – lack of air and circulation leads to
fibrosis and bronchiectasis

Obstructive Pulmonary Disease

Asthma
Emphysema (COPD)
Bronchitis (COPD)
Bronchiectasis (COPD)

Obstructive Lung Diseases

Obstructive disease is characterized by limitation of airflow usually resulting in an
increase in resistance from partial or complete obstruction at any level

Asthma
~ episodic
~ reversible bronchospasm
~ happens because of exaggerated bronchoconstrictor response
~ airway hyper-responsiveness to various stimuli
~ typically bronchodilate with epinephrine, which binds to adrenergic receptors
1) Extrinsic Asthma
~ anaphylactic – Type I hypersensitivity
~ Ab:Ag Rx – involving IgE , mast cells, histamine, eosinophils
~ IgE and eosinophiles are involved in allergies and parasites
~ mast cells degranulate and release histamine
~ histamine is involved in swelling, and it allows fluid to go from vessels into tissue
~ 3 types: atopic (skin), occupational (work related), allergic (peanut butter and shellfish
sandwich)
2) Intrinsic Asthma
~ non-immune triggers such as ASA (aspirin), pulmonary infections, psychological stress,
exercise
~ epinephrine and cortisol released in stress and exercise can cause inflammation
cascade
~ exercise can modulate the cortisol which may be beneficial if there is stress
COPD – Chronic Obstructive Pulmonary Diseases
Chronic bronchitis defined to be a chronic productive cough for at least 3 months in each
of 2 successive years for which other causes such as M. tuberculosis, lung carcinoma, or
chronic heart failure have been excluded
~ means that as long as you eliminate other disease that may lead to chronic bronchitis,
then the COPD is DUE to bronchitis and not a sequelae of something else

Emphysema defined to be abnormal, permanent enlargement of airspaces distal to

terminal bronchioles with destruction of walls without obvious fibrosis

COPD Risk Factors

Cigarette smoking and age – accounts for > 85% of risk of developing COPD
Air pollution – especially with chronic HT or LU disease
~ airborne chemical fumes or biologically inactive dust cause chronic airflow
obstruction
Hyperresponsive airways – atopic (allergic) state or a nonspecific airway
hyperresponsiveness
α-1 Antitrypsin deficiency – homozygous state
~ most associated with emphysema and less commonly with hepatic disease
~ trypsin breaks down proteins (usually in GI)
~ α-1 Antitrypsin is in the lungs and prevents us from “Eating our own lungs”

COPD – Emphysema Pathogenesis

Main Theories:
1) Protease/anti-protease imbalance – elastic fibers can be digested by elastase and α-1
Antitrypsin functions to oppose the elastase
2) Oxidant/anti-oxidant imbalance – ozone at ground level is not good for you because it
turns into reactive species and will become an antioxidant which causes peroxidation of
membranes
~ good anti-oxidants – Vitamins A, C, E and Selenium

COPD – Bronchitis Pathogenesis

Distinctive feature – smoking and pollution can cause hypersecretion of mucous – which
causes hypertrophy of mucous glands
~ causes inflammation with CD8+ T cells, macrophages and neutrophils
~ chronic inflammation leads to fibrosis and consequent narrowing of bronchioles
~ emphysema often occurs at same time as terminal bronchitis

COPD – Bronchiectasis
~ Permanent dilation of bronchi and bronchioles caused by destruction of muscle and
elastic support tissue
~ parts of some airways are dilated  mucous collects here  more prone to infection 
with infection you get inflammation  more obstruction
~ Not really a primary disease, but usually secondary to persistent infections, obstruction
or congenital conditions
~ There is focal or widespread pathology – can affect multiple lobes in one or two lungs
COPD – Bronchiectasis Pathogenesis
1) Chronic persistent infections – sever pneumonia d/t staph, strep pneumococci and
(esp in children) H influenzae and Pseudomonas aeruginosa
2) bronchial obstruction – any cause (foreign body, enlarged lymph node, mucus
inpaction, lung tumour)

COPD – Bronchiectasis Pathophysiology

~unilateral or bilateral; m/c in lower lobes
~ bronchial walls have extensive inflammatory destruction, chronic inflammation,
increased mucous, and loss of cilia
~ infection causes obstruction  lose alveolar area and fibrosis  decrease volume
in alveoli  decrease ability to oxygenate tissues  hypoxia  acid/base problems
 increase susceptibility to infection
~ generally associated with chronic bronchitis and/or emphysema and fibrosis
~ anastomoses b/w bronchial and pulmonary veins enlarge causing increase blood flow
 more venous blood means more CO2  which means hypoxic conditions  lead to
pulmonary hypertension  cor pulmonale late in disease
~ cor pulmonale refers to change in structure and function of RV of HT as a result of
respiratory disorder
~ RV hypertrophy is predominant change in chronic cor pulmonale
~ in acute cases – RV dilation
~ both hypertrophy and dilation are the result of increased pressure in RV

Restrictive Lung Diseases

Penumoconiosis
Goodpasteur’s
Other

Penumoconioses
Keep in mind that “oses” very often refers to the lungs, but there ARE exceptions
~ Deposition of particles in trachea and bronchi may include these 3 responses:
~ 1) bronchoconstriction: Ag-Ab Rx or from irritation as reflex mechanism
~ 2) bronchitis: mucous gland hypertrophy and can lead to minor chronic airflow
obstruction
~ 3) lung CA: d/t of asbestos fibers or dusts with adsorbed radon daughters

Silicosis
Pneumoconiosis caused by inhaling crystalline free silica (silicon dioxide, quartz, “rocky
stuff”)
~ get discrete nodular pulmonary fibrosis
~ in more advanced stages – see conglomerate fibrosis and respiratory impairment
~ conglomerate fibrosis – fibrosis’ clumped together

Coal Workers Lung

~ Diffuse nodular deposition of dust in lungs d/t long term exposure to bituminous or
anthracitic coal dust in mining
~ AKA coalminer’s pneumoconiosis, black lung disease or anthracosis
~ Caplan’s syndrome: anthracosis with RA (rheumatoid arthritis)

Asbestosis
Long term inhalation of asbestos dust
Risk developing asbestosis, lung CA, mesothelioma
Asbestos is promoter, but not initiator, of carcinogenesis
Incidence of LU CA increased in smokers with asbestosis

Asbestosis Pathophysiology
Individual fibers of asbestos are inhaled deep into lung parenchyma
~ may lead to development of diffuse alveolar and interstitial fibrosis
~ you don’t feel the pain because there is no Meissner’s corpuscles or Merkel’s discs
in the LU – only stretch receptors
Asbestosis causes reduction in LU volume, compliance (ability to inflate LU), and gas
transfer  chronically, can lead to hypoxia  acidosis (you get the idea…)

Malignant pleural and peritoneal mesotheliomas

Uncommon tumours of mesothelial tissue associated with abestosos exposure
Exposure usually occurs 15-40 years earlier, brief exposure, but heavy dose
Tumour is diffuse, infiltrates pleura widely, and always associated with pleural effusion
~ pleural effusion: xs fluid that accumulates in pleural cavity. Usually either one of 4
types of fluid: serous fluid (hydrothorax), blood (hemothorax), chyle (chylothorax),
pus (pyothorax)

Other Pneumoconioses
Berylliosis – Beryllium dust (Air plane manufacturing)
Byssinosis – bronchoconstriction occurring in cotton, flax, and hemp workers
Siderosis – iron dust

Sick Building Syndrome

~ Office employees in buildings that house many workers in proximity
~ New tight buildings – designed to reduce heat loss where windows don’t open and
HVAC (heating ventilation and air conditioning) ducts originate from a common source
~ Elevated CO2 is common cause
~ Also caused vehicles idling near air intakes, resulting in excessive exposure to carbon
monoxide and diesel fumes

Goodpasteur’s Disease
Hypersensitivity disorder of unknown cause
~ Anti-glomerular basement membrane antibodies in blood
~ Ab that attacks glomerulus in KI  damaged filtration
~ Linear deposition of immunoglobulin and complement in glomerular basement
membrane
~ Severe and progressive glomerulonephritis
~ Pulmonary hemorrhage
Pulmonary fibrosis
~ Often seen in diffuse parenchymal lung diseases
~ Affects the alveolar epithelium, pulmonary capillary endothelium, basement membrane,
perivascular and perilymphatic tissues
Causes:
~ inhaled stubstances: inorganic (asbestos, silica); organic (hypersensitivity pneumonitis)
~ drug induced: antibiotics, chemotherapeutic drug, antiarrhythmic drugs
~ connective tissue diseases: systemic lupus erythematosus, rheumatoid arthritis
~ infection: pneumonia, TB
~ indiopathic: sarcoidosis
~ certain malignancies
~ maybe autoimmune disorder??
Pulmonary fibrosis involves scarring of lung (above mentioned causes can all cause
scarring of lung)
~ Air sacs LU become replaced by fibrotic tissue  decreased oxygen  hypoxia 
acidosis

Sarcoidosis
Immune system disorder
Non-necrotising gramulomas (small inflammatory nodules) – caused by overactive
lymphocytes
Causes dysregulation of Vitamin D production
Macrophages inside the granulomas convert Vit D into its active form
~ too much 1,25-dihydroxyvitamin D can cause fatigue, lack of strength, irritability,
metallic taste, cognitive problems
No direct cause has been identified
~ maybe because bacterial infection
~ maybe hereditary
~ maybe environment

ARDS - Acute Respiratory Distress Syndrome

Serious reaction to different forms of injuries to lung
Leads to pulmonary edema
Inflammation of lung parenchyma leading to impaired gas exchange
~ at the same time, get systemic release of inflammatory mediators (cytokines)
~ causes: inflammation, hypoxemia (low O2 in blood)  organ failure
~ neutrophils and T-cells migrate to inflamed lung and get amplification of immune
response
~ get alveolar damage

Pneumonitis
~ hypersensitivity reaction
~ AKA extrinsic allergic alverolitis
~ inflammation of the alveoli within the lung caused by hypersensitivity to inhaled
organic dusts
~ characterized by the provoking antigen
~ can be acute or chronic